Iron constitutes an essential micronutrient in living organisms. All iron is absorbed
into the body through dietary intake, except for exogenous therapeutic sources. Dietary
iron is typically categorized as either heme or nonheme iron. Nonheme iron is essential
for regulating iron in the body, as it exists in various forms, including soluble
iron, storage iron within ferritin, and iron found in the catalytic centers of a wide
range of proteins. Iron homeostasis is carefully managed to ensure that sufficient
iron is available for critical biological processes while preventing the harmful effects
that can arise from excess iron. The small peptide hormone hepcidin is the main regulator
of iron homeostasis. Hepcidin and other iron regulatory molecules are regulated by
various signaling pathways, such as IL-6/JAK-STAT, BMP/SMAD, and MAPK. Alterations
in regulatory pathways may occur in response to iron accumulation or deficiency. Iron
overload in the body can activate JAK/STAT, BMP/SMAD and MAPK pathways, leading to
the initiation hepcidin synthesis. Conversely, in iron deficiency, as in hypoxic conditions
or EPO-mediated signaling pathways, HAMP synthesis in the nucleus is reduced. Thus,
this review provides an update on the possible regulatory pathways that play a role
in iron regulation and may be potential therapeutic targets.
